Pb2422: patients with high ebv viral load after allogeneic hematopoietic stem cell transplantation associate good prognosis when rapid immunosuppressants dose reduction can be achieved

Topic: 22. Stem cell transplantation - Clinical Background: After allogeneic hematopoietic stem cell transplantation (Allo-HSCT), EBV often causes reactivation. Sometimes, EBV reactivation progresses to lymphoproliferative disorder (LPD). Post-transplant risk factors for EBV reactivation include acute or chronic GVHD requiring intensive immunosuppressants (IMMs), high viral load, and mesenchymal stem cell therapy (Haematologica.2016;101:803). Evaluation of EBV reactivation is especially important. A definitive diagnosis of LPD can be made by biopsy, which is not easy depending on the patient’s general condition. Monitoring DNA in the peripheral blood is particularly useful in predicting the development of LPD. (Rev Med Virol.2020;30:e2108). Aims: Our aim was to analyze the clinical features and prognostic impact of EBV viral load status in Allo-HSCT recipients. Methods: A total of 121 consecutive patients who underwent Allo-HSCT between December 2011 and February 2022 at Japanese Red Cross Narita Hospital, Narita, Chiba, Japan, were included. And, we performed EBV DNA quantification after transplantation. EBV DNA quantification was performed in whole blood (WB). For EBV viral load analysis, cases in which EBV viral load was measured over time after transplantation were included in the study. This study grouped patients in which EBV DNA quantification reached >1000 copies/mL in WB during follow-up (N=50) and those who did not (N=71). And for the group that reached 1000 copies/mL or more, we analyzed the relationship between the rate of decline of IMMs and prognosis. Results: The median age of 122 patients was 53 years, and 64.5% was male. The underlying disease included AML/MDS, ALL, NHL/HL, and other diseases is 68.6%, 16.5%, 6.6%, and 8.3%, respectively. The group (N=50) with EBV DNA quantification higher than 1000 copies/mL had a higher percentage of ATG use than the group without it (52.0% vs 11.3%, p<0.001). In cases with EBV reaching >1000 copies/mL, 5/50 (10%) cases developed LPD and 6/50 (12%) cases used rituximab. IMMs reduction could be done after maximum EBV increase in 41/50 (82%) cases. And 30/50 (60%) cases could be achieved a 50% dose reduction or no restarting of IMMs within three months after maximum EBV increases. In cases in which EB virus DNA quantification reached >1000 copies/mL in WB, when stratified by the presence or absence of achievement of less than half IMMs within three months of maximum DNA detection, patients with the achievement of IMMs rapid dose reduction tended to have longer overall survival, OS (not reached vs 5.4 months, p＜0.001. Figure 1) and disease-free survival, DFS (88.4 months vs 5.3 months, p＜0.001). Moreover, rapid (in three months) IMMs dose reduction after increased EBV had significantly longer OS compared to those who can’t on multivariate analysis (hazard ratio: 4.07, 95% CI 2.28-7.27, p < 0.001). Although there were five cases of long-term persistence of high EBV viral load despite the end of IMMs, these cases coexisted peacefully with the patient without treatment with rituximab or chemotherapy. (The minimum number of days after SCT at maximum EBV increase was 266 days, and the maximum was 1143 days.) Summary/Conclusion: After detecting high EB virus viral load, OS and DFS were significantly inferior in patients who could not reduce IMMs by half or less within three months compared to those who could.Keywords: Epstein barr virus, Allogeneic hematopoietic stem cell transplant, Lymphoproliferative disorder